We have isolated and characterized a 100-120 kDa glycoprotein which serves as the receptor for mouse hepatitis virus, a murine coronavirus. Immunoaffinity purification of the receptor, cloning and expression of the receptor gene revealed that the receptor is a member of the immunoglobulin superfamily of glycoproteins, serologically related to proteins in the carcinoembryonic antigen family. A monoclonal antibody which binds to the receptor on mouse cells blocks MHV infection in vitro and partially protects mice from infection in vivo. We will characterize the domains of the receptor glycoprotein and the viral attachment glycoprotein which interact using recombinant DNA technology and protein chemistry as well as ultrastructural and X-ray crystallography. The information obtained will be used to develop drugs which interfere with the virus-receptor interaction, and these will be tested for protection from MHV infection in vitro and in a mouse model system. Analogous studies will be done to characterize the receptor for human coronavirus HCV229E which causes colds. Development of anti-receptor drugs may provide a useful approach to the prevention and treatment of coronavirus infections of man and animals.